The present invention relates to novel growth-promoting compositions and methods for their use. More particularly, the invention relates to compositions containing a mixture of anabolic substances.
With the ever-increasing demand for edible protein and the dwindling resources available for producing such protein, there has been considerable interest in developing bioactive substances which can increase the rate of growth or feed conversion efficiency in meat-producing animals. A group of naturally occurring substances that has received considerable attention includes the animal growth hormones.
Growth hormones are polypeptide anabolic hormones secreted by the pituitary glands of many species, including most meat-producing animals. Until fairly recently, growth hormones could be obtained only by extraction from animal tissues. These extraction procedures were arduous, and resulted in small yields of the hormone. With the advent of recombinant DNA technology, it has become possible to clone various animal growth hormone genes and produce the hormones microbially in useful yields at reasonable costs. See European Patent Application 83304574.3 (publication No. 0 103 395) to Biogen N.V.
Endogenous growth hormones stimulate growth, increase the rate of protein synthesis and the mobilization and utilization of fatty acids, and decrease the rate of carbohydrate utilization. Administration of exogenous growth hormones has been shown to increase the rate of growth, weight gain and meat production in animals. Although growth hormones are somewhat species specific, there is considerable homology among the amino acid sequences of animal growth hormones and these hormones have been shown to exhibit inter-species biological activities.
In addition to inter-species activities, various active fragments of growth hormones have been discovered. In particular, it has been found that polypeptides missing several amino acids from the N-terminus maintain a high level of biological activity. The aforementioned European Patent application discloses .DELTA.4 and .DELTA.9 constructions (missing 4 and 9 amino acids from the N-termini respectively) of bovine growth hormone which retain their biological activity. Moreover, biologically active animal growth hormones produced by recombinant DNA techniques often have an extraneous N-terminal methionine.
Another group of anabolic agents which has received a great deal of attention includes the "zearalins." "Zearalins" include zearalenone which is a natural metabolite of the organism Gibberella zeae and derivatives thereof. Zearalenone is described by Andrews, F. N., et al., U.S. Pat. No. 3,196,019. A number of active derivatives of zearalenone have been prepared and are described in the patent and technical literature. See Hidy, P. H., et al., Adv. Appl. Microbiol. 22, 59-82 (1979). Zearalin are resorcylic acid lactone derivatives. Zearalenone is represented by the following chemical formula: ##STR1##
U.S. Pat. No. 3,239,341 describes the reduction of the olefinic bond of zearalenone to produce zearalanone, and U.S. Pat. No. 3,239,345 describes the reduction of both the double bond and the ketone group of zearalenone to produce the compound, zearalanol. The latter compound has enjoyed considerable commercial success as an agent for improving weight gains and feed efficiencies in meat-producing animals. This compound is known by its common name, zeranol, and compositions containing the compound are sold under the trademark, Ralgro.RTM., by International Minerals and Chemical Corporation, Northbrook, Ill. U.S.A.